phase i study of cudc-101 with cisplatin and radiation in subjects with head & neck cancer

Conditions: Head and Neck Cancer

Summary: this is a phase i dose escalation study of cudc-101 in combination with concurrent cisplatin and radiation therapy in patients with locally advanced head and neck cancer. cudc-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (egfr), human epidermal growth factor receptor type 2 (her2) and histone deacetylase (hdac). the study is designed to establish the safety, tolerability and maximum tolerated dose (mtd) of cudc-101 when administered in combination with concurrent cisplatin and radiation over an 8-week treatment course, consisting of a one week run-in period of cudc-101 administered alone, followed by seven weeks of combination treatment with cudc-101, cisplatin and radiation therapy.


Eligibility criteria:
inclusion criteria: * subjects with locally advanced, pathologically confirmed diagnosis of squamous cell carcinoma of the head and neck at the following sites: oral cavity, oropharynx, hypopharynx and larynx with either: * stage iv p16 positive tumors and \>10 pack-years smoking history. * stage iii/iv p16 negative tumors, regardless of smoking history. * at least evaluable disease; one measurable site of disease according to recist (version 1.1) criteria (at least 10 mm for conventional ct/mri or spiral ct scan) is desirable. * subjects enrolled in the mtd expansion cohort must have at least 1 tumor lesion that is suitable for repeat biopsy (pre- and post-cudc-101 infusion). * age ≥ 18 years * ecog performance \< 2 * life expectancy ≥ 3 months * if female, neither pregnant nor lactating * if of child bearing potential, must use adequate birth control throughout the participation in the treatment phase and for 60 days following the last study treatment. * absolute neutrophil count ≥ 1,800/µl; platelets ≥ 100,000/µl; hemoglobin ≥ 8.0 g/dl, creatinine ≤ 1.5x upper limit of normal (uln); total bilirubin ≤ 1.5x uln; ast/alt ≤ 2 x uln. * serum magnesium and potassium within normal limits (may be supplemented to achieve normal values) * able to render informed consent and to follow protocol requirements. exclusion criteria: * prior radiotherapy to the region of the study cancer or adjacent anatomical sites, or \> 25% of marrow-bearing area. * prior chemotherapy for the current indication. * prior therapy that specifically and directly targets egfr, her2 or hdac. * use of investigational agent(s) within 30 days prior to study treatment. * primary tumor site of nasopharynx, sinuses, or salivary gland. * history of cardiac disease with a new york heart association (nyha) class ii or greater congestive heart failure (chf), myocardial infarction (mi) or unstable angina in the past 6 months prior to day 1 of treatment, serious arrhythmias requiring medication for treatment. * patients with prolonged qtc interval \>450 msec. * acquired immune deficiency syndrome (aids) or known infection with human immunodeficiency virus (hiv). testing is not required. * known history of gastrointestinal bleeding, ulceration, or perforation within 6 months prior to study treatment. * known history of stroke or cerebrovascular accident within 6 months prior to study treatment. * symptomatic cardiac conduction abnormality within 12 months prior to study treatment. * prior history of hearing impairment. * known history of renal disease or ongoing renal impairment. * any uncontrolled condition (such as active systemic infection, diabetes, hypertension), which in the opinion of the investigator, could affect the subjects participation in the study. * prior allergic reaction to cisplatin, carboplatin or other platinum-containing compounds. * central nervous system metastases.